Human oral biofilms are complex three-dimensional structures consisting of diverse and multispecies microbial communities formed on colonizable surfaces (Foster et al., 2004; Kolenbrander and London, 1993; Kolenbrander and Palmer Jr, 2004; Marsh and Bradshaw, 1995). Aside from the substrata's physical and chemical surface properties, which have a significant impact on bacterial accumulation (Quirynen et al., 2000), the formation of oral biofilms involves a series of events. This includes the initial formation of a conditioning saliva-derived film (the acquired salivary pellicle) on colonizable surfaces, the attachment of primary colonizers to host-derived receptor molecules present in the acquired pellicle, the subsequent interactions of secondary colonizers to the attached early colonizers, followed by the proliferation of the adhered bacteria (colonization), and the development of mature microbial communities (Kolenbrander and London, 1993; Marsh and Bradshaw, 1995; Quirynen et al., 2000). Uncontrolled growth of certain resident microbes in these communities may contribute to the development of oral diseases (Loesche, 1999).
The development of dental caries and periodontal diseases is closely associated with dental plaque, which is formed as a result of the adsorption of bacteria or their aggregates to the salivary pellicle formed on tooth surfaces. For the prevention and treatment of plaque-related oral diseases, there is a growing interest in the use of antimicrobial agents which act through bacteriocidal and/or bacteriostatic mechanisms. Among these agents are chlorhexidine, triclosan, metal ions, quaternary ammonium compounds and essential oils.
The salivary pellicle is formed through the selective adsorption of salivary proteins. The charged groups in the salivary proteins interact with charges of the opposite sign in the enamel and there is a predominance of negatively charged, acidic salivary proteins in the pellicle. Therefore, the affinity of the drug to teeth surfaces or acidic salivary proteins is an important factor for inhibiting the formation of plaque. Chlorhexidine is a bis-biguanide with strong cationic activity. It has been previously suggested that the binding of chlorhexidine to bacterial or acidic salivary components and subsequent retention on oral surfaces is directly related to the degree by which chlorhexidine can inhibit plaque growth. Although the chlorhexidine is regarded as the most efficacious antiplaque agent in current use, it has several disadvantages of bitter taste, impairment of taste perception, reversible staining of teeth and tongue and interaction with surfactants in the toothpastes.
In Applicant's co-pending application, U.S. Ser. No. 10/795,514, the contents of which are hereby incorporated by reference in its entirety, the present inventor discloses the discovery that the antimicrobial decapeptide KSL, and its analogs, may be used to prevent the formation of biofilms and may also be used to inhibit the growth of oral microorganisms.
While KSL showed usefulness in preventing the formation of oral biofilms, KSL did not have much affect on established biofilms. Moreover, while KSL was effective in inhibiting the growth of oral microorganisms, a reliable delivery method and treatment using KSL for oral hygiene had not been demonstratively shown. As will be appreciated, in situations where running water and toothbrushes are unavailable, methods of controlling plaque and oral biofilms are needed. For example, soldiers in the field may be asked to go days or weeks without brushing their teeth. Moreover, given the disadvantages of chlorhexidine, an antiplaque treatment having a more palpable taste with fewer side effects is needed to help ensure the treatment will actually be used.
The foregoing underscores some of the problems associated with treatment of established biofilms and using antimicrobial agents as an antiplaque agent. Furthermore, the foregoing highlights the long-felt, yet unresolved need in the art for a reliable formulation and method for treating established biofilms. The foregoing also highlights the long-felt, yet unresolved need in the art for a palpable formulation and method of treating plaque when brushing is impractical.